Abstract
Ornithine transcarbamylase deficiency (OTCD) is an X-linked urea cycle disorder with variable expressivity in heterozygous females. While liver function testing is often abnormal in patients with OTCD, liver failure is uncommon on presentation. A 13-month-old female with no significant past medical history presented with irritability, right arm weakness, and decreased appetite. Initial workup revealed hepatic dysfunction with an INR of 3.4, ammonia level of 75 μmol/L, and abnormal brain MRI with gyral edema with restricted diffusion, and patchy signal abnormality in basal ganglia. The MRI findings led to a putative diagnosis of acute disseminated encephalomyelitis prompting corticosteroid treatment. As steroid treatment was begun, she developed significant hepatocellular dysfunction with ALT 2,222 U/L, AST 630 U/L, prolonged INR, and elevated ammonia (213 μmol/L). Neurologic signs resolved and her ammonia level decreased (43 μmol/L) without further intervention; however, she had ongoing acute liver failure with coagulopathy and episodic irritability, managed as seronegative autoimmune hepatitis with partial response to corticosteroid therapy. At 18 months of age she presented with severe irritability with markedly increased ammonia (417 μmol/L). Plasma amino acids obtained several days prior to this acute episode demonstrated elevation in glutamine (2,725 μmol/L) and alanine (1,459 μmol/L). Biochemical testing demonstrated elevation of urine orotic acid (>240.6 mmol/mol creatinine). Genetic testing confirmed a heterozygous nonsense mutation in the OTC gene (c.958C>T, R320X). After treatment with ammonia scavengers and a protein-restricted diet, hepatic function normalized and irritability resolved. The diagnosis of a urea cycle disorder should be considered in patients with unexplained hepatic dysfunction.
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Communicated by: Johannes Hðberle
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Synopsis
Urea cycle disorders can present with hepatic failure, and early recognition of a urea cycle disorder in the differential of hepatic dysfunction can prompt early metabolic diagnosis to initiate specific lifesaving metabolic treatment.
Contributions of Individual Authors
Farrah Rajabi drafted the initial manuscript and approved the final manuscript as submitted.
Lance H. Rodan and Gerard T. Berry assisted in drafting, and revised the manuscript and approved the final manuscript as submitted.
Maureen M. Jonas, Janet Soul, Nicole J. Ullrich, Ann Wessel, Susan E. Waisbren, and Wen-Hann Tan reviewed and revised the manuscript and approved the final manuscript as submitted.
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Farrah Rajabi, Lance Rodan, Maureen M. Jonas, Janet Soul, Nicole J. Ullrich, Ann Wessel, Susan E. Waisbren, Wen-Hann Tan, and Gerard T. Berry declare that they have no conflict of interest.
This is a descriptive report, and all patient information has been anonymized to ensure patients are not identifiable. All patients have provided informed consent to genetic testing. This chapter does not contain any studies with human or animal subjects performed by any of the authors.
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Rajabi, F. et al. (2017). Liver Failure as the Presentation of Ornithine Transcarbamylase Deficiency in a 13-Month-Old Female. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 40. JIMD Reports, vol 40. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2017_55
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DOI: https://doi.org/10.1007/8904_2017_55
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